Biomedical subjects

T Kikuchi

Publications and source records attributed to T Kikuchi.

At least 253 records · Page 14Linked to original sources

PubMed1997

Antioxidant, OPC-14117, attenuates edema formation and behavioral deficits following cortical contusion in rats.

Oxygen free radicals may contribute to tissue injury processes in the central nervous system following ischemia or trauma. Recent studies have suggested that inhibition of free radicals improves the outcome in experimental models involving such conditions, and antioxidant therapy appears promising. In the present study, behavioral changes and edema formation in rat cortical contusion model were investigated, and the effects of a superoxide radical scavenger, OPC-14117, were tested. Wistar rats were anesthetized with halothane inhalation. Cortical contusion was induced in the parietal cortex employing a controlled cortical impact device. Immediately following injury induction, OPC-14117 was administered (300 mg/kg, p.o.). Edema formation was assessed in the center and peripheral areas of the contusion by the specific gravity method. Behavioral changes were evaluated by the Morris water maze test and the habituation of exploratory activity. The results revealed that the vehicle-administered control showed progressive edema formation and behavioral deficits following the injury. These changes were significantly attenuated by the OPC-14117 treatment (p < 0.05). Further, OPC-14117 reduced the size of contusional necrosis (p < 0.05). These findings suggest that superoxide free radicals are involved in contusion-induced edema formation, necrosis formation, and behavioral deficits, and that OPC-14117 has a therapeutic potential to prevent secondary cell damage following traumatic brain injury.

Animals↗

PubMed1997

A keratin K10 gene mutation in a Japanese patient with epidermolytic hyperkeratosis.

Epidermolytic hyperkeratosis (EHK), or bullous congenital ichthyosiform erythroderma, is characterized by generalized erythroderma, ichthyosiform skin and blistering, and is caused by an aberration of the keratin intermediate filaments. In this study, we examined keratin K10 and 1 gene mutations in a Japanese EHK patient who had severe ichthyosiform erythroderma at birth and developed subsequent blistering. The patient had a G to A transition at codon 156 of the keratin K10 gene, which resulted in an arginine (Arg)-->histidine (His) substitution in the helix initiation peptide of the highly-conserved 1A domain in keratin K10. This is the first mutation report of a Japanese patient with EHK, although the position and mode of the mutation identified here did not differ from those in reported Western cases.

Amino Acid Sequence↗

PubMed1997

The attenuating effect of carteolol hydrochloride, a beta-adrenoceptor antagonist, on neuroleptic-induced catalepsy in rats.

It is known that beta-adrenoceptor antagonists are effective in the treatment of akathisia, one of the extrapyramidal side effects that occur during neuroleptic treatment. Neuroleptic-induced catalepsy, a model of neuroleptic-induced extrapyramidal side effects, was considered suitable as a model for predicting neuroleptic-induced akathisia in humans, although neuroleptic-induced catalepsy was not considered a specific test for neuroleptic-induced akathisia. Therefore, the effects of carteolol, a beta-adrenoceptor antagonist, on haloperidol-induced catalepsy in rats were behaviorally studied and compared with those of propranolol and biperiden, a muscarinic receptor antagonist. Carteolol, as well as propranolol and biperiden, inhibited the haloperidol-induced catalepsy. The inhibitory effect of carteolol was almost comparable to that of propranolol, but was weaker than that of biperiden. Carteolol did not evoke postsynaptic dopamine receptor-stimulating behavioral signs such as stereotypy and hyperlocomotion in rats. Carteolol did not antagonize the inhibitory effects of haloperidol on apomorphine-induced stereotypy and locomotor activity in rats. In addition, carteolol did not evoke 5-HT1A receptor-stimulating behavioral signs such as flat body posture and forepaw treading and did not inhibit 5-hydroxytryptophan-induced head twitch in rats. Finally, carteolol did not inhibit physostigmine-induced lethality in rats. These results strongly suggest that carteolol improves haloperidol-induced catalepsy via its beta-adrenoceptor antagonistic activity and is expected to be effective in the treatment of akathisia without attenuating neuroleptic-induced antipsychotic effects due to its postsynaptic dopamine receptor antagonistic activity.

Adrenergic beta-Antagonists↗

PubMed1997

An in-frame deletion in peripheral myelin protein-22 gene causes hypomyelination and cell death of the Schwann cells in the new Trembler mutant mice.

Cloning and sequencing of the peripheral myelin protein-22 cDNA and genomic DNA from newly found Trembler mice revealed an in-frame deletion including exon IV which codes for the second (TM2) and a part of third (TM3) transmembrane domain of peripheral myelin protein-22. This mutation was distinct from those in both other allelic Trembler and Trembler-J mice, which carry point mutations within the putative transmembrane spanning regions of peripheral myelin protein-22. Inheritance was autosomal dominant. The affected mice revealed an abnormal gait, which appeared at 15-20 days of age, followed by motor and sensory ataxia, which remained throughout life. Most of the affected mice could survive more than one year. One of the most notable pathological phenotypes was a giant vacuolar formation in the sciatic nerve of homozygotes. They vary in size within the cytoplasm of Schwann cells, which failed to assemble myelin at any ages studied. Heterozygotes showed normal myelination during the early postnatal stages, followed by a segmental demyelination at an advanced stage. Vacuolar formation was not so frequent as in the homozygotes. These results suggest that the missing of transmembrane spanning region (TM2 and TM3) of peripheral myelin protein-22 may disturb a dual biological function of peripheral myelin protein-22, leading to a dysmyelination of axons and to a vacuolar formation within the cytoplasm of the Schwann cells. The latter phenotype is discussed in conjunction with the disruption of an intracellular transport system and subsequent cell death.

Animals↗

PubMed1997

In vitro and in vivo antiproliferative effects of simvastatin, an HMG-CoA reductase inhibitor, on human glioma cells.

We analyzed the antiproliferative effect of simvastatin (SV), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on human glioma cell lines. Inhibition of cell growth with SV was observed in all cell lines tested. Different culture conditions altered this inhibition of growth: the lower the concentration of fetal bovine serum (FBS) in the medium, the higher the inhibitory effect of SV on glioma cells. On morphological examination, we found that most of the cells exposed to SV became rounded and the proportion of floating cells was increased in a time-dependent manner. Then we examined whether exogenously added mevalonic acid reversed the growth inhibitory effect of SV. Exogenous mevalonic acid suppressed the inhibitory effect of SV on glioma cells in a dose-dependent manner. SV also enhanced the expression of low-density lipoprotein (LDL) receptor on glioma cells. We also found that peroxidized LDL (p-LDL) was cytotoxic to glioma cells and that SV had additive effects on pLDL-induced cytotoxicity. In a mouse model, growth of glioma cells inoculated into nude mice was inhibited by intratumoral injection of both SV and peroxidized LDL. These results indicate that mevalonic acid or a metabolite in the cholesterol synthesis pathway is necessary for the growth of glioma cells and that simvastatin and/or peroxidized LDL should be examined further as potential therapeutic agents for gliomas.

Animals↗

PubMed1997

Criteria of normal blood pressure and hypertension in Japanese preschool children.

The blood pressure (BP) of 5332 Japanese preschool children from 2 to 6 years of age was measured using an automated BP recorder (Dinamap Model 8104). The third reading of the consecutive measurement of BP was used for analysis. This study adopted a definition of hypertension developed by The Task Force conducted in the United States in 1987, which showed the 95th percentiles of systolic and diastolic BP for age and sex. Stepwise regression analysis revealed that body height, weight and heart rate had significant effects on both systolic and diastolic BP, whereas age had an effect on diastolic BP only, while sex and area where the subjects lived did not affect either BP. The 95th percentiles of systolic/diastolic BP at 2, 3, 4, 5, and 6 years of age were 115/69, 113/68, 114/65, 118/67 and 116/69 mm Hg in boys, and 121/70, 114/69, 115/67, 118/68 and 120/69 mm Hg in girls, respectively. The BP of Japanese preschool children can be evaluated using the data shown in this study.

Age Factors↗

PubMed1997

Megakaryocytes derived from CD34-positive cord blood cells produce interleukin-8.

In a serum-free liquid culture, thrombopoietin (TPO) selectively stimulated the growth of megakaryocytic cells from CD34-positive cord blood cells. Using these cultured cells, we investigated cytokine production by human megakaryocytes. Day 10 megakaryocytes (2 x 10(5)) secreted > 1000 pg/ml of interleukin (IL)-8, in contrast to small amounts of IL-1beta and IL-6. A time-course study showed that the IL-8 production of megakaryocytes occurred at the late phase of the culture period. The megakaryocyte-conditioned medium had the chemotactic potential of polymorphonuclear leucocytes, which was abrogated by the addition of anti-IL-8 antibody, suggesting the secretion of biologically active IL-8. The combination of TPO and IL-1alpha was required for a significant augmentation of the IL-8 secretion. Direct evidence for IL-8 synthesis in megakaryocytes was provided by reverse transcription-polymerase chain reaction on purified CD41b+ cells and by the detection of intracellular IL-8 in CD41b+ cells. These results suggest that TPO stimulates not only the proliferation and differentiation of the progenitors capable of megakaryocytic lineage expression but also IL-8 release by the megakaryocytic cells with the aid of IL-1.

Cells, Cultured↗

PubMed1997

Predominant expression of a Z-chromosome-linked immunoglobulin superfamily gene, ZOV3, in steroidogenic cells of ovarian follicles and in embryonic gonads of chickens.

A cDNA clone, pZOV3, was isolated from the cDNA library of immature chicken ovaries and its gene was mapped to the middle of the short arm of the Z chromosome. The cDNA sequence suggests that ZOV3 is a novel member of the immunoglobulin superfamily. cDNA clones of homologues of chicken ZOV3 were also obtained from Japanese quail and pigeon. Northern blot hybridization suggests that the high-level expression of the ZOV3 gene is restricted to the gonads: embryonic, immature and mature ovaries, and embryonic and immature testes. Western blot analysis and immunocytological detection using specific polyclonal antibodies against amino- and carboxyl-terminal regions of ZOV3 demonstrate that ZOV3 is a plasma membrane-bound glycoprotein that exists in granulosa cells and islets of cells in the theca externa layer of ovarian follicles. The latter islets coincide with those producing estradiol-17 beta. In male and female embryos, production of ZOV3 is first prominent in medullary and seminiferous codes, respectively, of developing gonads. Then, after hatching, it is shifted to the cortex surrounding the primitive follicles in the ovary or is continued weakly in the primary seminiferous tubules in the testis. Expression of the ZOV3 gene and production of ZOV3 are no longer detectable in the mature testis. ZOV3 is unique among the immunoglobulin superfamily proteins in that it is produced predominantly in gonads. Its possible role in differentiation or maintenance of steroidogenic cells in an ovarian follicle is discussed.

Amino Acid Sequence↗

PubMed1997

Effects of ketamine and pentobarbitone on acetylcholine release from the rat frontal cortex in vivo.

We have studied the effects of ketamine and pentobarbitone on acetylcholine (ACh) release from the rat frontal cortex using microdialysis. Ketamine 25, 50 and 100 mg kg-1 increased ACh release from the frontal cortex to 286%, 253% and 381% of basal release, respectively. In contrast, pentobarbitone 10, 20 and 40 mg kg-1 caused 73%, 78% and 96% inhibition of basal levels, respectively. The results suggest that ketamine and pentobarbitone have opposite effects on ACh release from the rat frontal cortex, as seen previously in the rat hippocampus.

Acetylcholine↗

PubMed1997

Prediction of the biologically active sites in eclosion hormone from the silkworm, Bombyx mori.

The structure-activity relationship of eclosion hormone from the silkworm, Bombyx mori, was analyzed. First, the probable active residues in silkworm eclosion hormone and also tobacco hornworm eclosion hormone were predicted by the average distance map method. To examine the contributions of those residues to the activity of silkworm eclosion hormone, Gly-substituted mutants for those predicted residues were produced by site-directed mutagenesis and their activities were evaluated by a bioassay. Finally, Glu12, Met24 and Phe25 were estimated to be the crucial residues for the eclosion hormone activity. The possibility of the development of a blocker of an eclosion hormone receptor on the basis of the present work is also discussed.

Amino Acid Sequence↗

PubMed1997

The relationship between fatty liver and hyperinsulinemia in obese Japanese children.

BACKGROUND: Previous reports have revealed that fatty liver involving obesity is closely related to insulin resistance or hyperinsulinemia in adulthood. This study investigates the importance of hyperinsulinemia in obese children with fatty liver. METHODS: The subjects were 228 obese children 6 to 15 years old in Niigata Prefecture, Japan. The serum level of glutamic pyruvic transaminase (GPT) was evaluated as an indicator of fatty liver. The effects of their percent obesity (percent over ideal body weight), Rohrer index (g/cm3), skinfold thickness, percent body fat measured by bioelectrical impedance analysis, total cholesterol (TC), high-density lipoprotein cholesterol, triglyceride (TG), blood glucose, and immuno-reactive insulin (IRI) on GPT were evaluated using regression analyses. RESULTS: The incidence of fatty liver (GPT over 35 IU/I) was 24.1% in this study. In simple regression analyses, percent obesity, Rohrer index, skinfold thickness, TC, TG, blood glucose, and IRI correlated positively with GPT (p < 0.05). In stepwise regression analysis including these seven variables, the predictive equation for GPT as a function of IRI alone accounted for 24.2% of the total variance of GPT. The addition of TC alone, and TC and percent obesity together increased the coefficients of determination to 28.4% and 29.9%, respectively. Rohrer index, skinfold thickness, Tg, and blood glucose were not taken as related variables with GPT. CONCLUSION: Hyperinsulinemia is an important contributor to the development of fatty liver, apparently more than anthropometric data, blood glucose, or serum lipids in childhood obesity.

Adolescent↗

PubMed1997

Two families of Lowe oculocerebrorenal syndrome with elevated serum HDL cholesterol levels and CETP gene mutation.

The ocuolocerebrorenal syndrome of Lowe (OCRL) is an X-linked recessive disorder which is characterized by renal tubular dysfunction, congenital cataracts, and cognitive impairment. In a review article by Charnas et al. (N Engl J Med 1991; 324: 1318-25), hypercholesterolemia, due to elevated high-density lipoprotein cholesterol (HDL-C) levels, was described as being highly prevalent in OCRL patients. This report prompted us to examine three OCRL children in two unrelated families and we confirmed the high prevalence of high serum HDL-C levels in the patients (3/3). In addition, we found that their normal family members also had high serum HDL-C levels (5/7). Analysis of cholesteryl ester transfer protein (CETP) genes, which are now recognized as one of factors increasing serum HDLC levels, revealed the D442G mutation in exon 15 in 5 of 10 family members (1/3 of OCRL patients and 4/7 healthy family members), and no mutation of intron 14 G(+1)-to-A. The detected D442G mutation may be one of the causes in our two OCRL families; however, further studies, based on larger numbers of subjects, are needed to confirm these findings.

Adolescent↗

PubMed1997

Inhibition of TSH-induced hydrogen peroxide production by TNF-alpha through a sphingomyelinase signaling pathway.

Tumor necrosis factor-alpha (TNF-alpha) has been suggested to be related to the pathogenesis of autoimmune thyroid diseases, nonthyroid illness, and other thyroid dysfunctions induced by infectious diseases. In relation to these, in vitro studies demonstrated that TNF-alpha influences growth and/or differentiated functions mediated by thyroid-stimulating hormone (TSH), including 125I organification. In the present study, we found that TNF-alpha inhibits TSH-induced H2O2 production, which is an inevitable process for iodide organification, and hence thyroid hormone synthesis, in FRTL-5 thyroid cells. In the cells, TNF-alpha induced ceramide production and the addition of exogenous ceramide or sphingomyelinase treatment of the cells simulated TNF-alpha actions. Although TSH stimulation of H2O2 production is mediated by the phospholipase C (PLC)-Ca2+ pathway, TNF-alpha and exogenous and endogenous ceramide affected neither TSH-dependent PLC activation and Ca2+ mobilization nor TSH-induced cAMP accumulation but attenuated Ca(2+)-induced H2O2 production. We conclude that TNF-alpha, through a sphingomyelinase-ceramide pathway, regulates TSH-induced H2O2 production at steps beyond the Ca2+ mobilization step in the PLC-Ca2+ signaling pathway coupled to TSH. This suggests participation of TNF-alpha in thyroid disorder in hormone synthesis induced by thyroid disease associated with the activation of immune systems.

Animals↗

PubMed1997

Bacterial pneumonia causes augmented expression of the secretory leukoprotease inhibitor gene in the murine lung.

The cDNA of murine secretory leukoprotease inhibitor (SLPI) was cloned from a mouse lung cDNA library. The amino acid sequence deduced from the cDNA showed 58 and 51% homology with those of human and porcine SLPI, respectively. A two-domain structure with similar amino acid sequences, four intradomain disulfide bonds, and high proline content, which are characteristics common to human and porcine SLPI, was also found in the mouse protein. The amino acid residues for the signal sequence and active site are also conserved in mouse SLPI. RNase protection assay showed the expression of the SLPI gene in liver, intestine, spleen, and epididymis, suggesting the distribution of SLPI in tissues other than lung and seminal vesicles. In the lung infected with Streptococcus pneumoniae strain FP1284, 10 h after inoculation of bacteria the number of SLPI mRNA transcripts was three times higher than baseline. The increased level of expression remained constant for at least 48 h. This result clearly contrasts to that obtained for spleen, in which the SLPI mRNA transcript level was mostly unchanged during the course of pneumonia. These facts suggested the local regulation of the SLPI gene expression in vivo in response to inflammatory stimuli at the site of inflammation.

Amino Acid Sequence↗

PubMed1997

Cis-acting region associated with lung cell-specific expression of the secretory leukoprotease inhibitor gene.

Secretory leukoprotease inhibitor (SLPI) is a serine protease inhibitor, produced locally in respiratory and genital glands, but not in the liver. In the present study the promoter region of this gene was analyzed to better understand the molecular mechanisms involved in transcriptional regulation. DNase-I hypersensitive sites were detected within 1 kbp upstream of exon I in chromatin structures of type II pneumocyte cell line A549 and utero-cervical cell line HeLa, both of which express SLPI mRNA transcripts. The function of the SLPI promoter encompassing these DNase-I hypersensitive sites has been studied by deletion analysis with the luciferase gene as a transient expression vector. In this analysis, we found three transcription control regions that function in A549 cells but not in nonlung cell lines, such as HeLa and hepatoma Hep G2. Among three cis-regulatory regions, a proximal 41-bp region (-132 to -92 bp relative to the transcription start site) is responsible for the most striking magnitude of transcriptional activity. This region corresponds to the transcriptional activating sequence detected in another lung cell line, HS-24, indicating that this 41-bp sequence is required for lung cell-specific expression. An electrophoretic mobility shift assay demonstrated that this 41-bp promoter region contains an 11-bp recognition sequence for two nuclear binding proteins, one of which is abundant in lung cell lines, and the other in nonlung cell lines. These results suggest that the ratio of these two nuclear binding proteins confers the cell type specificity on the expression pattern of the SLPI gene.

Adenocarcinoma↗

PubMed1997

Role of collagen in retinoic acid-induced differentiation and down-regulation of TGF-beta receptors in rat preosteoblastic RCT-1 cells.

Retinoic acid induces differentiation of preosteoblastic cells. We have demonstrated that osteoblastic differentiation and down-regulation of transforming growth factor (TGF)-beta receptors requires the interaction of type I collagen with alpha 2 beta 1 integrin (J Biol Chem 271: 3938-3944, 1996). The purpose of this study was to clarify the role of collagen in retinoic acid-induced differentiation and down-regulation of TGF-beta receptors using preosteoblastic RCT-1 cells. Retinoic acid enhanced the expression of alkaline phosphatase and type I collagen, and reduced TGF-beta receptors in these cells. Inhibiting collagen synthesis abolished these changes. Because TGF-beta inhibits osteoblastic differentiation, the changes described here may contribute to the osteoblastic differentiation by retinoic acid.

Alkaline Phosphatase↗

PubMed1997

Presence of anti-pituitary antibodies and GAD antibodies in NIDDM and IDDM.

OBJECTIVE: To evaluate the clinical significance of the presence of anti-pituitary antibodies (APAs) in patients with NIDDM or IDDM and to examine the relationship of APAs to GAD antibodies (GADAs). RESEARCH DESIGN AND METHODS: Serum samples were obtained from patients with NIDDM and IDDM. APAs, determined by Western blot analysis, and GADAs, determined by radioimmunoassay, were detected in the patients' sera and control sera. Urinary levels of C-peptide (U-CPR) were measured. RESULTS: The prevalence of APAs was significantly higher in patients with NIDDM (24.2%) or IDDM (56.8%) than in healthy control subjects (6%). In patients with NIDDM, the levels of U-CPR were significantly lower, and the prevalence of insulin deficiency was higher in APA+ patients than in APA- patients. CONCLUSIONS: This is the first study to demonstrate that the prevalence of APAs is increased in patients with NIDDM and IDDM. The presence of APAs may be related to reduced secretion of insulin in NIDDM patients.

Adolescent↗

PubMed1997

Effect of verbal cues on recognition memory and pleasantness evaluation of unfamiliar odors.

The experiment investigated the effect of verbal cues on recognition memory for unfamiliar odors. 58 participants learned 20 odors of chemical substances. The control group learned the odors without accompanying verbal labels whereas two other groups learned the odors with accompanying verbal labels. The labels referred to relatively pleasant or unpleasant odor sources. On a memory test, administered 15 min. and also 1 wk. after the learning phase, participants were asked to recognize 10 learned odors from 10 unlearned odors and to evaluate each odor's pleasantness. Analysis showed (a) the verbal labels did not facilitate recognition of the unfamiliar odors, (b) recognition performance was lower after 1 wk. than after 15 min., and (c) rated pleasantness tended to be affected by the verbal label assigned to the odor in the learning phase.

Cues↗